Project Summary Within the past decade, electronic cigarettes (e-cigs) have become commercially available in the US, rapidly growing in popularity; 13% of adults in the US have used an e-cig and 4% are habitual ?vapers?. E-cigs are typically used for recreation or as a pathway to complete cessation. The usage of e-cigs has caused widespread debate within the public health community, mainly because there is little scientific evidence regarding their safety. On one hand, if e-cigs are safer than conventional cigarettes, they may be used as a cessation device, potentially reducing the number of smoking-related mortalities (20% of deaths in the US is linked to smoking, resulting in an estimated $500 billion in economic damage per year). However, if e-cigs usage is linked to adverse health consequences, regulatory standards must be enforced to avoid severe health impacts, especially in cigarette-naive groups. While recent efforts have been directed to uncovering potential consequences of e-cig aerosol exposure on acute pulmonary and cardiovascular function, to date minimal scientific evidence exists regarding the long-term impact of e-cig vaping on the cardiovascular and pulmonary systems. To address this need, the main goal of this study is to evaluate and compare the short and long term pulmonary and cardiovascular health consequences of e-cig vaping and cigarette smoking in a well-established murine model of atherosclerosis, specifically addressing the ?Health Effects? category of the seven FDA CTP scientific interest areas. To accomplish our study objectives, we propose the following specific aims: (1) link dosimetry with inflammation-mediated pathological changes in the vasculature, heart, and lungs, and (2) assess the health benefits of complete smoking cessation versus switching to e-cig usage on the cardiovascular and pulmonary systems. This study is significant because it will (1) combine state-of-the-art computational and experimental methodologies to determine both the cardiovascular and pulmonary health effects of e-cigs, compared to conventional cigarettes, (2) provide a correlation matrix linking predicted deposition concentrations with inflammatory response and cardiovascular and respiratory structure and function. This novel pipeline may be extended in future studies to translate findings from mouse to human. By combining our strengths and expertise in bioengineering, computational modeling, medical imaging, and cardiovascular tissue mechanics, we will provide strong quantitative measures on the health effects of e-cig usage, with the goal of providing scientific evidence for FDA regulations.